Skip to main content
. 2020 Sep 18;11(9):1091. doi: 10.3390/genes11091091

Table 2.

Metabolomic studies in FD.

Subjects Sample Type Methods Used Outcomes Reference
42 FD patients, 48 healthy controls random urine LC-MS/MS The total urinary concentration of lyso-Gb3 and its analogues: 100% specific for classical and non-classical FD patients. [110]
18 asymptomatic females, 18 symptomatic females, 27 males, 16 control urines, 58 control plasmas plasma and urine UPLC-MS/MS Urinary ceramide dihexoside (CDH):

  • more prominent glycosphingolipid in females

  • elevated isoforms of Ga2 with 10 different longer chain can detect asymptomatic heterozygotes better than Gb3 and lyso-Gb3.

 [113]
34 untreated and 33 treated Fabry males, 54 untreated and 19 treated females, 34 males and 25 female healthy control random urine UPLC-MS/MS Validated method for separation of 12 most abundant Ga2 isoforms/analogs from their lactosylceramide (LacCer) counterparts:

  • urinary LacCer significantly higher in female than males

  • after normalization with creatinine, higher the Ga2(C24:0) urinary level in the untreated males comparing to the the untreated female

 [114]
15 untreated and 28 treated Fabry males, 21 untreated and 10 treated Fabry females, 15 males and 26 female healthy control plasma UPLC-MS/MS Validated UPLC-MS/MS method for the multiplex analysis of lyso-Gb3 and its 6 analogs. [115]
16 untreated Fabry males, 16 healthy Fabry males random urine TOF MS Untreated FD patients: 22 urinary Ga2 isoforms/analogs; quantification of Ga2 and Gb3 urinary isoforms/analogs that were elevated in untreated Fabry males. [111]
9 males with classic FD, 7 males with later-onset FD, 10 females, 5 males with functional variants, 40 healthy controls plasma nano-LC-MS/MS Plasma lyso-Gb3: higher in all subgroups of FD, especially in patients whose disease stage had proceeded.
Detection of eight lyso-Gb3-related analogues: lyso-Gb3(-12) and lyso-Gb3(+14) for the first time. Majority of the FD patients had elevated plasma concentrations of the lyso-Gb3 analogues, especially lyso-Gb3(-2).		 [116]
55 pediatric Fabry patients, 26 healthy pediatric controls, 108 adult Fabry patients, 16 healthy adult controls random urine UPLC-MS/MS Pediatric FD patients:

  • lyso-Gb3 (+16) the most reliable for the diagnosis of pediatric FD females, whereas lyso-Gb3 (−12), lyso-Gb3(+16) and lyso-Gb3 (+34) for males

  • children had lower urinary lyso-Gb3 levels than adults.

 [112]
74 Fabry patients, 41 healthy controls plasma UPLC-MS/MS Lyso-Gb3 and related analogues in plasma:

  • higher in FD males compared to females

  • higher in untreated males compared to treated males

  • decreased after the beginning of ERT in a Fabry male.

 [109]
114 Fabry patients, 34 healthy controls plasma TOF MS Fabry patients: three new lyso-Gb3 analogs (m/z ratios at 802, 804, and 820) with higher relative concentration in males compared to female patients. None was detected in the majority in healthy controls. [102]
24 Fabry patients, 8 healthy controls plasma TOF MS Identification and characterization of five novel analogues/isoforms of Gb3 [101]
164 Fabry patients, 94 healthy controls random urine HPLC-MS/MS Further analysis of 7 previously discovered lyso-Gb3-related biomarkers:

  • not detected in healthy controls

  • higher excretion levels in Fabry males compared to females

  • correlation with ERT status in males

 [117]
16 male Fabry patients, 16 healthy control males random urine TOF MS 15 isoforms/analogs of Gb3:

  • variable urinary quantities of Gb3-related metabolites in untreated Fabry males

  • identification of methylated Gb3-related analogs

 [118]
63 untreated Fabry patients, 59 healthy controls random urine TOF MS Seven novel urinary biomarkers (mass-to-charge ratios (m/z) of 758, 774, 784, 800, 802, 820, and 836)

  • none were detected in controls

  • higher concentrations in males with FD compared to females.

  • decreased excretion of all lyso-Gb3-related analogs after ERT in male FD patients

[100]

MS, mass spectrometry; TOF, time-of-flight; LC-MS/MS, liquid chromatography coupled to tandem mass spectrometry UPLC-MS/MS, ultra-performance liquid chromatography coupled to tandem mass spectrometry; HPLC-MS/MS, high-performance liquid chromatography coupled to tandem mass spectrometry.